Philip O. Katz

Apparent complete lower esophageal sphincter relaxation in achalasia

Seven of 23 patients (30%) seen in 2 yr with clinical and radiologic manifestations of achalasia underwent esophageal manometry demonstrating aperistalsis but apparent complete lower esophageal sphincter (LES) relaxation. Detailed clinical and laboratory evaluation suggests these patients may represent an early stage of achalasia. Duration of dysphagia and weight loss were significantly less (p less than 0.05), whereas LES pressure was similar in the 7 patients compared with the 16 more traditional achalasia patients. Isotope retention during radionuclide esophageal solid-emptying studies showed intermediate delay in emptying between normal subjects and achalasia patients. The duration of LES relaxation in this group was significantly shorter (p less than 0.01) than in normal subjects. Although complete, sphincter relaxation in these patients is functionally inadequate and may be the result of this shortened duration. The small size of standard manometry catheters may also contribute to this confusing finding. Apparent complete LES relaxation may be seen during manometry in achalasia and should not exclude its diagnosis.

Pneumatic dilatation is effective long-term treatment for achalasia.

Although pneumatic dilatation (PD) has been anestablished treatment for achalasia for decades, thereis limited information on its long-term clinicalefficacy. We have followed up the clinical status of patients having PD with a 30- or 35-mm balloonby one of us (D.O.C.) over a 25-year period. Of 144patients whose initial records were available forreview, 31 could not be contacted. Of the remaining 113 patients, 72 (64%) responded to a questionnaireassessing swallowing status and patient satisfaction,and this forms the basis of this report. There were 32men and 40 women, with mean age 46 years (range: 17-78); mean length of follow-up since PD was6.5 years (range: 10 months to 25 years). Success wasprimarily defined by the need for no additional therapyfor achalasia other than one or two PDs. PD was effective long-term treatment in 61/72 patients(85% ); only four of these required a second PD overthis time interval. There was no significant differencein any of the following parameters between patients with a treatment success or failure: age, sex,size of pneumatic dilator, and duration of symptomsprior to PD. Response was significantly better (P <0.05) in patients having no prior dilatation (43/47; 91%) than in those in whom another physicianhad performed prior dilatation (18/25; 72%). In responseto the question of whether they would select PD again,68 patients (94%) responded positively. In conclusion, pneumatic dilatation performedusing a consistent technique by an experienced physicianis effective long-term therapy for achalasia patients ofall ages. Most patients require only onedilatation.

Globus sensation is associated with hypertensive upper esophageal sphincter but not with gastroesophageal reflux

Globus sensation (globus) is best described asa constant feeling of a lump or fullness in the throat.Although the etiology of globus remains unclear, it hasbeen attributed to a hypertensive upper esophageal sphincter (UES) resting pressure and togastroesophageal reflux (GER). The aim of this studywas, therefore, to determine if significant associationsexisted among globus, UES resting pressure, and GER. We reviewed the records of all patients who hadstationary esophageal manometry over a 21 -year intervalwith specific attention to symptoms of globus, UESpressures, and ambulatory pH studies. Patients with hypotensive UES (<30 mm Hg) wereexcluded. Chi square (χ2) test was usedto determine significant associations. Six hundred fiftypatients had normal UES resting pressures and 101patients had hypertensive UES (>118 mm Hg). Seventeen ofthe 650 (3%) (16 women/1 man; mean age: 48, range 32-81years) with normal UES described globus. Conversely, 28of the 101 (28%) (15 women/13 men; mean age: 43, range 23- 61 years) patients withhypertensive UES described globus. There was asignificant association between hypertonicity of the UESand globus (χ2 = 93.42, P < 0.0001).In patients with normal UES, globus occurred predominantly infemales (χ2 = 6.33, P < 0.01).Twenty-three (16 women/7 men; mean age: 43, range 23-60years) of the 45 patients with globus had priorambulatory pH studies. Six of 23 (26%) had GER. Compared to an age-,sex-, and UES-pressure-matched group of 23 patients (16women/7 men; mean age: 44, range 22-75 years) withoutglobus, nine (39%) had GER, thus showing no significant association of globus with GER (P = 0.35).There also was no significant association of GER withnormal UES or with hypertensive UES in these patients.In conclusion, there is a significant association between hypertensive UES and globus. The datasuggest two possible etiologies: female patients withnormal UES pressure potentially having increasedafferent sensation and a group with equal sexdistribution but abnormally elevated UES resting pressure.This study does not support GER as an etiology ofglobus.

Prior Sensitization of Esophageal Mucosa by Acid Reflux Predisposes to Reflux-induced Chest Pain

Esophageal acid exposure is believed to be a major source of unexplained chest pain; but, individual episodes of reflux in pH study are not consistently associated with chest pain. Our aim was to discover whether prior sensitization of esophageal mucosa by acid reflux predisposes to reflux-induced chest pain. Ambulatory pH studies of patients referred to our laboratory from January 1991 to November 1996 with noncardiac chest pain was reviewed. We compared the frequency of esophageal acid exposure in the 30 minutes preceding chest pain episodes with a positive symptom/reflux association (+SRA) to reflux with the frequency of acid exposure in the 30 minutes preceding those chest pain episodes that were not associated with reflux negative symptom/reflux association (−SRA). We analyzed the time esophageal pH <4, symptom index (SI) defined as percentage of chest pain episodes associated with reflux in the preceding 5 minutes, and amount of reflux in the 30 minutes preceding each chest pain episode. Of 104 patients, 52 had chest pain during their pH study, 10 had high SI (≥50%), and 42 had low SI (<50%). Those with a high SI were significantly more likely to have an abnormal pH study (p = 0.015). Chest pain associated with reflux in proceeding 5 minutes (+SRA) was strongly associated (p < 0.002) with additional reflux episodes in the preceding 25-minute period. Chest pain related to reflux is associated with sensitization of the esophageal mucosa by prior reflux events.

Nocturnal acid breakthrough: pH, drugs and bugs.

• Nocturnal acid breakthrough (NAB) (i.e. at least 60 consecutive minutes of intragastric pH < 4 during the overnight period) occurs in greater than 70% of patients on proton pump inhibitor (PPI) therapy. • Intragastric pH control by PPIs in H. pylori-positive patients is superior compared with their H. pylori-negative counterparts. • Bedtime histamine-2 receptor antagonists (H2RA) can control NAB on PPI twice-daily better compared with an additional bedtime dose of PPI. • Further studies are warranted to evaluate whether infection or drugs should be considered to control NAB. Nocturnal acid breakthrough (NAB) was defined by Peghini et al. in 1998 as the presence of at least 60 continuous minutes of intragastric pH < 4 during the overnight period (22:00–06:00 h) in patients taking a proton pump inhibitor (PPI) twice-daily before meals. NAB was shown to occur in more than 70% of patients on PPI therapy but can be decreased or eliminated by adding a histamine-2 receptor antagonist (H2RA) at bedtime. Helicobacter pylori status influences intragastric acid control on PPI therapy: H. pylori-positive patients having better gastric acid control compared with their H. pylori-negative counterparts. Recent data indicate that NAB might not occur in H. pylori-positive subjects on twice-daily PPI, suggesting there is no need for combined PPI twice-daily and H2RA therapy to control night-time gastric acid secretion in these individuals. The clinical importance of NAB has been debated ever since this concept was introduced. The importance of NAB in healthy subjects and asymptomatic, uncomplicated gastro-oesophageal reflux disease patients on PPI therapy may be low, but ignoring it in patients with poor oesophageal motility and Barretts oesophagus may result in suboptimal treatment. Further studies are warranted to investigate whether leaving H. pylori to ‘assist’ acid suppression obtained by PPI twice-daily, adding bedtime H2RAs after successful H. pylori eradication or other approaches to eliminate NAB results in better clinical outcomes.

Lessons learned from intragastric pH monitoring.

Management of gastroesophageal reflux disease (GERD) is based on the concept that gastric contents, principally acid and pepsin, are responsible for esophageal injury and symptoms of reflux disease. Pharmacologic management in the year 2001 revolves around the basic principle that control of intragastric pH correlates with esophageal healing and, subsequently, symptom relief. Although the majority of patients respond to a single daily dose of a proton pump inhibitor, many patients with reflux disease are “refractory” even to twice daily doses of these drugs. Potential reasons for this less than optimal response can be found when carefully examining the intragastric pH responses of healthy subjects and patients with GERD to these agents when taken at various times of the day, in proximity to meals, and in higher doses. In the past several years, we have explored many of these issues in attempting to understand the mechanisms behind incomplete response to proton pump inhibitors, using combined intragastric and intraesophageal pH monitoring. The “lessons learned” from these and supportive studies are the subject of this review.

Diffuse esophageal spasm: not diffuse but distal esophageal spasm (DES).

Diffuse esophageal spasm is an uncommon motility disorder that is found in less than 5% of patients undergoing esophageal motility testing for dysphagia. It is defined manometrically by the presence of 20% or more simultaneous contractions in the distal esophageal body with normal peristalsis. This motility abnormality has been traditionally identified as occurring primarily in the smooth muscle portion of the distal esophagus yet, the term “diffuse” persists in the medical literature to identify DES. The aim of our study was to assess the diffuse or limited nature of this entity by evaluating the prevalence of simultaneous contractions in both proximal and distal esophagus in patients with DES. We reviewed esophageal motility tracings of 53 consecutive patients (32 F, 21 M) with DES and compared them with 53 age-matched patients with manometric normal studies. In the distal esophagus we found 195 simultaneous contractions (37% of swallows) with a median of 3 and range of 2–7 per patient. Of the 53 patients with DES a total of 13 simultaneous contractions (2% of swallows) occurred in the proximal esophagus with only 3 (5.6%) of the 53 patients having 2 or more simultaneous contractions in 10 swallows. None of the patients with normal manometry showed more than one simultaneous contraction in either proximal or distal esophagus. In conclusion, these findings suggest that the term diffuse esophageal spasm is a misnomer and the DES is more appropriately described as “distal” esophageal spasm.

Acid-Induced Esophagitis in Cats Is Prevented by Sucralfate but not Synthetic Prostaglandin E

The cytoprotective effects of liquid sucralfate and a synthetic analog of prostaglandin E1 (PGE1) on acid-induced esophagitis in cats were studied. Esophagitis was induced in adult cats using a constant infusion of 0.1 N HCl at 1 ml/min for 20 min. Animals were infused for either one or three days. Mucosal lesions were evaluated by blinded investigators using both fiberoptic endoscopy and light microscopy. Histologic changes included basal cell hyperplasia, intraepithelial leukocytosis, and subepithelial leukocytosis. Liquid sucralfate given prior to acid infusion consistently prevented acid-induced lesions in both one- and three-day infusions, demonstrated by both endoscopy and quantitative histologic scoring. Indomethacin (200 μg/kg) given prior to sucralfate and acid did not affect sucralfate cytoprotection. Synthetic PGE1, given in doses of 5 μg/kg and 100 μg/kg, afforded no esophageal cytoprotection. These studies indicate that sucralfate is cytoprotective against acid-induced esophageal injury in cats, an effect that does not appear to be mediated by prostaglandin. In addition, synthetic PGE1 does not confer protection in this animal model.

Incidence, predictors, and outcomes of gastrointestinal bleeding in patients on dual antiplatelet therapy with aspirin and clopidogrel.

Objectives The benefits of dual antiplatelet therapy are counterbalanced by the increased incidence of gastrointestinal (GI) complications. The aim of this study was to determine the frequency of GI bleeding, identify the predictors associated with the increased bleeding, and determine the short-term and long-term outcomes. Methods This was an observational, case-control cohort study carried out at the Albert Einstein Medical Center. It included all patients who had a drug-eluting stent implanted between May 2003 and April 2007. A total of 1852 patients were identified; of these 50 patients were readmitted for a GI bleed. A control group of 202 patients who did not have any evidence of GI bleeding were compared with the original group. All data were expressed as mean±SD. The baseline clinical characteristics between the 2 groups were compared using the t test and the Fisher exact test. Multivariate analysis was used to determine the predictors of GI bleeding. Results The rate of GI bleeding was 2.7%. The mean age in the group with GI bleeding was 70.9±12.2 years, whereas in the group without GI bleeding it was 66.5±12.8 years (P<0.05). The majority of the patients presented with melena (40%). Gastritis and gastric ulcers were the most common findings seen in 49% of the patients on endoscopy. On multivariate logistic regression analysis, a history of GI bleeding was the most important independent predictor of future GI bleeding (P<0.001), whereas the use of statins was found to be protective (95% confidence interval, 0.13-0.48; P<0.001) against future GI bleeding. The 30-day mortality rate in the GI bleeding and control groups was 3.7% and 0%, respectively (P<0.01), whereas in the corresponding 1 year the mortality rate was 18.9% and 0%, respectively (P<0.001). Conclusions The rate of GI bleeding in patients on dual antiplatelet therapy is low. Earlier history of GI bleeding is the most significant multivariate predictor of future GI bleeding whereas statins seemed to be protective. Patients with GI bleeding have increased short-term and long-term mortality; thereby a history of earlier GI bleeding needs to be assessed carefully before starting dual antiplatelet therapy. This may play a vital role in the selection of therapeutic strategies in these patients.

Comparison of potential cytoprotective action of sucralfate and cimetidine: Studies with experimental feline esophagitis

The potential mucosal protective effects of a liquid sucralfate preparation and the histamine (H2)-antagonist cimetidine on acid-induced esophagitis were studied. Esophagitis was induced in adult cats using a constant infusion of 0.1 N hydrochloric acid at 1 ml/minute for 20 minutes. Mucosal lesions were evaluated by blinded investigators using both fiber-optic endoscopy and light microscopy. Histology was scored for basal cell hyperplasia, intraepithelial leukocytosis, and subepithelial leukocytosis. Liquid sucralfate given prior to acid infusion consistently prevented acid-induced lesions, demonstrated by quantitative histologic scoring. Although cimetidine did not show the same degree of protection as sucralfate, the results did show a trend towards a cytoprotective effect.